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A型唾液酸酶对小鼠的急性和亚急性毒性():器官特异性损伤与免疫反应

Acute and Subacute Toxicity of Sialidase From Type A in Mice (): Organ-Specific Damage and Immune Response.

作者信息

Silaen Otto Sahat Martua, Nugroho Christian Marco Hadi, Kurnia Ryan Septa, Widyaningtyas Silvia Tri, Wayan Teguh Wibawan I, Sasmono R Tedjo, Soebandrio Amin

机构信息

Doctoral Program in Biomedical Science, Faculty of Medicine, University of Indonesia, Jakarta 10430, Indonesia.

Animal Health Diagnostic Unit, PT Medika Satwa Laboratoris, Bogor, Indonesia.

出版信息

Vet Med Int. 2025 Jul 1;2025:5582663. doi: 10.1155/vmi/5582663. eCollection 2025.

Abstract

Sialidases, enzymes produced by Type A, play a critical role in cleaving sialic acid residues essential for viral entry into host cells. By targeting pathogens such as coronaviruses, influenza, and paramyxoviruses, sialidase represents a promising therapeutic candidate. While in vitro studies confirm its efficacy against influenza, evaluating its safety profile in vivo is imperative. This study investigates the acute and subacute toxicity of sialidase from Type A in BALB/c mice (). Acute toxicity involved a single intranasal dose followed by a 14-day observation, while subacute toxicity encompassed daily doses for 30 days. Mice were administered 187.5, 375, or 750 mU/mL of sialidase, with saline as the control. No mortality or overt toxicity occurred, but significant histopathological alterations were evident in the lungs and liver at higher doses. Observed effects included lung inflammation and edema, liver congestion, and kidney inflammation. Hematological analysis revealed immunosuppressive effects, including reduced white blood cell and lymphocyte counts, alongside dose-dependent IL-6 expression changes. Sialidase doses of 187.5 and 375 mU/mL were deemed safe, whereas toxicity became pronounced at 750 mU/mL.

摘要

唾液酸酶是A型产生的酶,在裂解病毒进入宿主细胞所必需的唾液酸残基方面发挥着关键作用。通过靶向冠状病毒、流感病毒和副粘病毒等病原体,唾液酸酶是一种有前景的治疗候选物。虽然体外研究证实了其对流感的疗效,但评估其在体内的安全性至关重要。本研究调查了A型唾液酸酶在BALB/c小鼠中的急性和亚急性毒性()。急性毒性涉及单次鼻内给药,随后进行14天观察,而亚急性毒性包括连续30天每日给药。给小鼠施用187.5、375或750 mU/mL的唾液酸酶,以生理盐水作为对照。未发生死亡或明显毒性,但在较高剂量下,肺和肝脏出现了明显的组织病理学改变。观察到的影响包括肺部炎症和水肿、肝脏充血以及肾脏炎症。血液学分析显示有免疫抑制作用,包括白细胞和淋巴细胞计数减少,以及剂量依赖性的白细胞介素-6表达变化。187.5和375 mU/mL的唾液酸酶剂量被认为是安全的,而在750 mU/mL时毒性变得明显。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7502/12237549/74e35b90fc9a/VMI2025-5582663.001.jpg

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